Parasitic diseases are the most widespread of all the major human diseases currently affecting about three billion people. Effective drug treatment is nonexistent for many of them, and most of the available drugs, when adequately tested, have been shown to have mutagenic, cytotoxic, and carcinogenic activities. In recent years it becomes increasingly apparent that many reactive intermediates of xenobiotics are free radicals. The formation of free radicals, including oxygen-derived radicals, may lead to extensive cellular damage. The consequences of radical-initiated reactions may be the immediate death of the cells or may be more subtle and delayed as evidenced by the development of neoplasms. The aim of this investigation is: (a) To identify free radical intermediates generated by antiparasitic drugs by direct electron spin resonance spectroscopy or by spin-trapping techniques, and (b) to investigate the ability of parasite and mammalian cells and their subcellular fractions to generate free radicals from antiparasitic compounds. This information would help make future drug development possible on a more rational basis than has been possible hitherto. In addition, the study of the mode of action of existing chemotherapeutic and chemoprophylactic agents is necessary to maximize efficacy and to minimize toxicity.